America's First Therapeutic Cancer Vaccine

By William Haseltine

Last Thursday the Food and Drug Administration approved Provenge for the treatment of advanced prostate cancer. Provenge is the first therapeutic vaccine to be approved in the U.S. for cancer treatment, ushering in what may be a new era in immune-based cancer treatments. Approval marks the successful conclusion of a 20-year odyssey with some remarkable twists and turns.

My part of the story begins with research on HIV/AIDS while I was a professor at Harvard Medical School and the Dana Farber Cancer Center. By the early 1980s, it was known that HIV was transmitted sexually between men and women. Because the virus was also transmitted by blood via contaminated needles, infection during sex was also thought to be blood-related, occurring through small tears in the mucosal tissue.

I began to question this explanation when I read a report documenting seven women that were infected by a single donor during artificial insemination.I began to ask all the scientists I knew if they had ever heard of cells that travel back and forth across mucous membranes. I suspected that such cells, if they existed, might carry the virus into the body across intact membranes.

Eventually people directed me to Ralph Steinman at Rockefeller University. For many years Ralph had been working with a specialized type of immune cell called dendretic macrophages. He proposed that these cells play a key role in immunity, that they are the first cells to recognize foreign substances and are the "master educators" of the immune system. At the time, this revolutionary idea, now accepted to be true, was vigorously rejected by most immunologists. This debate aside, what interested me was the observation that dendretic macrophages were know to travel back and forth across the mucosal membrane of the cervix.

Eric Langhoff, a young Danish doctor who had been trained by Ralph Steinman, joined my laboratory to work on this problem. Within a short period of time we were able to demonstrate that dendretic macrophages were highly efficient carriers of HIV. The virus sticks tightly to these cells and is carried across the mucosal membrane to nearby lymph nodes. The dendretic cells educate other immune cells by touching them with their long diaphanous membranes. This is how the virus reaches the susceptible immune cells, called CDA or T cells. Now inside the body, it begins the infection.

In the course of this work I learned much about these unusual cells. I learned they could be taught to educate the immune system outside the body. This could be done by exposing purified dendretic cells to a foreign substance and then reintroducing them back into the body. No other cells had this ability.

This observation triggered another thought. Might it be possible to train purified dendretic cells to recognize cancer cells? If so, then reintroduction of these cells might train the body's own immune system to attack the cancer itself.

At the time I was a consultant to a venture capital company, Healthcare Ventures. I presented the outline of this idea and they agreed to provide $5 million to fund a new company to explore this new approach to anti-cancer therapy. As often happens, I was not alone with this idea. While attending a scientific conference in Holland, I met two physicians scientists from Stanford, Sam Strober and Ed Engelmann. They had independently come up with the same idea and were in the early stages of starting a similar company. We joined forces, and Activated Cell Therapy, Inc., was born.

It is now 20 years on. The company experienced many ups and downs. It moved from California to Washington near Seattle. New financing was needed. Other venture capital companies provided additional funding. The original management was replaced. The name was changed to Dendreon. The company raised money from the public markets. I moved on to genomics research, and Sam and Ed's role as advisors ended. But the vision remained. The scientists, doctors and management at Dendreon persisted despite skepticism and initial rejection by the FDA.

The treatment is now approved. This small step in cancer treatment for men with advanced prostate cancer provides new hope for all those with cancer. We have begun to realize the dream of harnessing the power of the immune system to fight cancer. The road to here has been long and circuitous, but the path ahead is clear.